Non-steroidal anti-inflammatory drugs (NSAID) are drugs with analgesic and antipyretic effects. NSAIDs can be classified based on their chemical structure, including propionic acid derivatives, acetic acid derivatives and enolic acid derivatives, inter alia. Propionic acid derivates include ibuprofen, naproxen and ketoprofen. Ketoprofen, one of the most potent NSAIDs, is well known for treating symptoms associated with chronic arthritis, osteoarthritis, acute tendonitis, bursitis, headaches, migraines, chronic neuropathic pains, shingles, premenstrual symptoms, sports injuries and like.
Traditionally, ketoprofen has been marketed in various tablet dosage forms. However, tablets may not be suitable for juvenile, certain general public and geriatric populations who have difficulty in swallowing. The requirement of additional water and oral liquids to facilitate swallowing further hampers the successful administration of tablet dosage forms in the aforementioned patient populations.
Edible oral strip/wafer thin film (hereinafter “oral thin film”) dosage forms for delivering active pharmaceutical agents are one avenue by which to facilitate self-administration of medications and enhance patient compliance and adherence. Edible oral film strip dosage forms generally incorporate an active ingredient into a thin film for subsequently delivery, which is conventionally delivery primarily via the oral mucosa. The edible oral film strip dosage forms more specifically incorporate clinically active pharmaceutical ingredients which can be easily dispersed and disintegrated in the saliva of the oral cavity without water or additional oral liquids to allow for easy swallowing. To date, only a very small number of edible oral film strip dosages are commercially available that incorporate therapeutically active pharmaceutical ingredients, however.
Unfortunately, ketoprofen has an unpleasant bitter taste with a burning sensation, limiting its incorporation into edible oral film strips. Ketoprofen also irritates the throat mucosal membrane during swallowing. However, in view of recently renewed interest for clinically proven and safer pain medications due to Cox 2 inhibitor's unwanted side effects, the successful development of an edible oral strip/wafer thin film dosage form containing Ketoprofen is of significant commercial interest.
Heretofore, those skilled in the at have considered the development of an edible oral film strip dosage form containing ketoprofen to be an exceptionally intricate formulation challenge. Particularly, it has been heretofore understood by those skilled in the art that the complete masking of the bitter taste and burning sensation of ketoprofen would not be possible.
United States Patent Application Publication No. 2002/0169212 discloses an animal health solution formulation of ketoprofen in water. The solution medication is prepared by solubilizing ketoprofen with a weak base in water. A weak base and Ketoprofen in a ratio of 10 to 1 were utilized to solubilize the ketoprofen in water. Additional flavoring and sweetening agents were added to the aqueous ketoprofen solution to increase the palatability of the solution. This publication, however, does not disclose a dosage form containing a taste masked Ketoprofen active.
International Patent Application No. WO 2007/109057 A2, whose United States equivalent is United States Patent Application Publication No. 2007/0292515, discloses a thin film dosage form using Ketoprofen as the active ingredient that has been neutralized with an edible alkaline agent(s) to mask the unpleasant taste of the Ketoprofen. This publication does not utilize alternate and multiple synergistic taste masking strategies to further and completely mask the unpleasant taste of Ketoprofen, however. In regard, in early 2005 the instant inventors performed tests which determined that the neutralization of Ketoprofen using ordinary laboratory edible alkaline agents, such as those used in WO 2007/109057, could not block the entirety of the unpleasant tastes of Ketoprofen successfully.
Therefore there remains a strong need in the art to develop a more robust edible oral film strip dosage forms that can deliver unpalatable active pharmaceutical ingredient(s), such as unpalatable NSAIDs, in the oral cavity. There particularly remains a strong need in the art to develop edible oral film strip dosage forms that eliminate the adverse bitter taste, burning sensation and throat irritation of ketoprofen.